USP Monograph: Poloxamer

Poloxamer is a nonionic triblock copolymer (PEO–PPO–PEO): a central hydrophobic poly(oxypropylene) chain flanked by two hydrophilic poly(oxyethylene) chains. It is widely used as an excipient—emulsifier, solubilizer, surfactant/wetting agent, and stabilizer—across oral, topical, and parenteral dosage forms. Common USP–NF types include Poloxamer 124, 188, 237, 338, and 407, which differ by molecular weight and oxyethylene/oxypropylene composition.

The USP–NF Poloxamer monograph sets official tests and acceptance criteria for identity, composition, and quality for multiple types (124, 188, 237, 338, 407). When an excipient is labeled “NF/USP,” it is expected to conform to the applicable monograph and General Notices; in the U.S., drugs with names recognized in USP–NF must meet compendial standards or risk being deemed adulterated/misbranded.

• Definition & Composition. General formula HO(C₂H₄O)ₐ(C₃H₆O)ᵦ(C₂H₄O)ₐH; each type has specified ranges for average molecular weight, weight % oxyethylene, and unsaturation (mEq/g). Examples:
  • Poloxamer 188: MW 7680–9510; %OE 81.8 ± 1.9; unsaturation 0.026 ± 0.008.
  • Poloxamer 407: MW 9840–14,600; %OE 73.2 ± 1.7; unsaturation 0.048 ± 0.017. 

• Identification. Infrared (IR) absorption; spectrum matches the appropriate USP Poloxamer Reference Standard (Liquid RS for 124; Solid RS for 188/237/338/407).

• Assays (composition).
  • Average Molecular Weight by end-group titration with phthalic anhydride/pyridine (calculations per monograph).

• Weight Percent Oxyethylene by quantitative ¹H-NMR (integrals near ~1.08 ppm and 3.2–3.8 ppm). 

• Unsaturation. Titrimetric procedure with specified acceptance per type.

• Residual volatile impurities are subject to strict safety-critical limits: free ethylene oxide NMT 1 µg/g; propylene oxide NMT 5 µg/g; and 1,4-dioxane NMT 5 µg/g, all determined by compendial GC headspace methods. These limits apply to all compendial grades.

• pH. 5.0–7.5 in a 1 in 40 aqueous solution (per <791>). 

• Elemental impurities. Controlled per USP <232>/<233> (earlier monograph prints referenced Heavy Metals <231>, but this limit is obsolete; compliance is now required via elemental impurity risk assessment under <232>/<233>).